Sasha Pantel

TL;DR: DEMETER, an analytical framework that segregates on- from off-target effects of RNAi, demonstrates the basis behind one such predictive model linking hypermethylation of the UBB ubiquitin gene to a dependency on UBC and provides a foundation for a cancer dependency map that facilitates the prioritization of therapeutic targets.

TL;DR: CERES, a computational method to estimate gene-dependency levels from CRISPR–Cas9 essentiality screens while accounting for the copy number–specific effect, is developed and found that CERES decreased false-positive results and estimated sgRNA activity for both this data set and previously published screens performed with different sg RNA libraries.

TL;DR: It is found that the number of CRISPR/Cas9-induced DNA breaks dictates a gene-independent antiproliferative response in cells, which has practical implications for using CRISpr/cas9 to interrogate cancer gene function and illustrate that cancer cells are highly sensitive to site-specific DNA damage, which may provide a path to novel therapeutic strategies.

TL;DR: CERES, a computational method to estimate gene dependency levels from CRISPR-Cas9 essentiality screens while accounting for the copy-number-specific effect, as well as variable sgRNA activity, is developed and applied to sets of screens performed with different sgRNAs and found that it reduces false positive results and provides meaningful estimates of sg RNA activity.

TL;DR: Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer.